Hydrogels have been widely investigated for a variety of biomedical applications, particularly as scaffolds offering a 3-dimensional (3D) microenvironment for tissue regeneration. Hydrogels have been used for 3D cell culture and tissue regeneration because of their high water content resembling the aqueous microenvironment of the natural extracellular matrix (Seliktar, 2012) and tunable biochemical and physicochemical properties (Burdick and Anseth, 2002; Williams et al., 2003; Silva et al., 2004). While many properties of natural hydrogel matrices are modifiable, their inherent isotropic structure limits the control over cellular organization that is critical to restore tissue function.
Previous studies have primarily focused on exploring the mechanical and biochemical versatility of hydrogels and elucidating their impact on cellular activities (Engler et al., 2006; Discher et al., 2005; Lutolf et al., 2003; Dalsin et al., 2003; Martino et al., 2009). A lack of methodologies exists, however, for engineering anisotropic topographical cues in hydrogels to control the 3D spatial patterns of encapsulated cells. As a result, controlling topographically induced cell alignment and migration has not been readily achieved for hydrogel matrices, even though such cellular manipulation on 2D substrates has been shown to be important in controlling cell organization, tissue microarchitecture, and biological function (Yang et al., 2005; Bettinger et al., 2009; Chew et al., 2008; Aubin et al., 2010).
Recently, Kang et al. reported a microfluidic-based alginate hydrogel microfiber with a surface alignment feature produced by solution extrusion through a grooved round channel, and demonstrated guided neurite outgrowth for neurons cultured on the surface of the microfibers (Kang et al., 2011). This alignment cue, however, is only confined to the surface of the microfibers. Zhang et al. have generated peptide nanofiber hydrogels with long range nanofiber alignment through heat-assisted self-assembly of amphiphilic peptide molecules and mechanical shear (Zhang et al., 2010). Although the resulting aligned nanofiber “noodles” effectively induced cellular alignment in 3D, this method is only applicable to specific peptide materials.
On the other hand, cellular alignment mediated by 2D electrospun nanofiber matrices has been shown to effectively promote stem cell differentiation and cellular functions (Lim and Mao, 2009; Ji et al., 2006). Although dispersing solid polymer nanofibers into the hydrogel matrix has been used to generate a composite scaffold (Coburn et al., 2011), controlling alignment of the nanofibers inside a hydrogel matrix is challenging.